EXECUTIVE INTERVIEW – Aptar Pharma: From Self-Injection to Auto-Injection

The global market for injectable drugs is valued at US $240 billion, representing some 28% of the global drug market, with an annual growth rate of +4% in 2012. In addition, the pipeline of new injectable drugs is very healthy, with more than 3,500 ongoing projects, of which the vast majority are for generics with very few biosimilars (generics of off-patent biopharmaceutical drugs) so far. Pierre Carlotti, Vice-President of Marketing and Communication for Aptar Pharma Prescription Division, recently spoke with Drug Development & Delivery about the market for auto-injectors and some relevant market trends, and explains how his company went about designing and developing a novel auto-injector.

Q: How did Aptar Pharma become interested in the injectable drug delivery devices market? Could you tell our readers more about this new strategy?

A: Aptar Pharma is the Aptargroup business segment dedicated to meeting the needs of biotechnology, healthcare, and pharmaceutical companies with innovative and patient-focused drug delivery solutions. Our core technologies and businesses have traditionally been non-invasive spray and aerosol drug delivery devices, including electronically assisted devices. We are world leader in the pharma spray and aerosol market, manufacturing more than 1 billion proprietary devices per year, which are regulated as combination drug products, in our facilities in Asia, EU, Latin America, and North America.

Recently, we reoriented our strategy to also increase our market presence in the large and fast-growing biopharmaceutical market in which injectable devices are the gold standard dosage forms. In 2011, we sealed a strategic partnership with Oval Medical, a cutting-edge parenteral technology company based inCambridge, UK. In 2012, we acquired the French company Stelmi (now rebranded as Aptar Stelmi), a world-leading supplier of premium quality elastomeric closures for parenteral primary packaging. These deals will allow us to combine Aptar Pharma’s recognized experience, industry leadership, and global presence with Oval Medical’s expertise and Aptar Stelmi’s 50-year track record, to become a leading player in high-quality injectable devices and components.

Q: Could you tell us more about the specific auto-injector segment of the injectable drug market that Aptar Pharma is targeting?

A: Auto-injectors are spring-loaded devices holding a prefilled syringe (the primary drug container) that are easy to use by design and intended for self-administration of a fixed dose by the patient, even if in some cases they are used by less trained personnel (eg, relatives of the patient).

They represent a tiny niche of the injectable drug market because they are used in only a few drug categories designed to treat selected chronic diseases. These include rheumatoid arthritis, lupus, psoriasis, spondilarthritis, multiple sclerosis, hepatitis C, anemia, and emergency/crisis treatments, such as anaphylactic shock and migraine attacks. Given the ageing of the global population and other pathophysiologic factors, the prevalence of these diseases is growing. There are also other diseases that could benefit from auto-injectors in the future, including specific indications in asthma, cancer, and cardiovascular therapies.

Currently, this small niche represents a device market worth US $130 million in 2012 – disposable and reusable auto-injectors combined – with a very dynamic annual growth rate of more than 20%.

The drug delivery device is key because it defines the user interface: there is no “good drug” without a “good device.” As a consequence, self-injection requires an adapted device user interface (the “one-size-fits-all” device technology platform does not exist), and proper training and instructions for use. This is particularly true in the case of non-chronic diseases, or when the treatment regimen dictates infrequent drug administration (eg, once every 2 or 4 weeks).

In addition, as novel injection devices are sophisticated pieces of technology with strong intellectual property protection, they are “enabling drug delivery technologies”. They enhance ease of delivery in the hands of the patient (if cognitive, perceptual, and physical abilities are not too impaired by the disease) and thus reinforce patient compliance. They also sustain market differentiation, which is strategic for pharmaceutical companies to gain or protect market share. Self-injection devices are also more cost effective for the healthcare system.

Q: Pro-Ject™ (Figure 1) is
Aptar Pharma’s new auto-injector: can you tell us how it was designed and developed?

A: It is essential that all key stakeholders involved in the decision-making process are consulted early on in the development of a novel auto-injector. Patients and healthcare professionals are pivotal partners because they are the interface with the drug product and the device. Although pharmaceutical and biopharmaceutical companies are the natural partners of device manufacturers, it is essential for the latter to listen to, understand, and take into account the “voice of patients and healthcare professionals” so as to capture user needs, preferences, and potential misuses as early as possible. Human Science Engineering is now part of the device development process to define and refine the User Requirement Specifications in accordance with the latest regulators’ guidelines.

The healthcare professional’s point-of-view: Physicians are not device specialists, but they are the main prescribers. Training nurses have a pivotal role in informing, assisting, and training patients to best use the prescribed device, especially when it is used for treating chronic diseases, such as rheumatoid arthritis. Their job is complex given the variety of device technologies and operating modes, user interfaces, look and feel, as well as the variety of patient and therapy profiles. Ideally, they contribute their professional advice, training, and monitoring to reinforce patient adherence, which in the end is essential for the success of the therapy.

The patient’s point-of-view: Patients are not device specialists either, but they are the regular users in the case of self-administration. Self-injection is not an easy experience, especially when the drug is painful; and it is dependent on the drug regimen. A variety of improper uses of auto-injectors have been reported, including upside-down firing, premature device firing, and removal that have significant safety and efficacy consequences. Usability is often reported as a main issue given the variety of unlocking (cap removal or push-on-skin) and firing mechanisms (activation button or slider or push-on-skin), which may confuse patients, especially when they shift from one drug product to another, which can involve a change of auto-injector. The feedback provided by the device to the patient may vary as well, with single-click and double-click audible cues, see-through control window for visual cues, and various other visual and tactile indicators.

Pro-Ject(TM) integrates all the identified user-preferred features. It has all the attributes of a “modern” disposable auto-injector designed around a standard glass prefilled syringe (PFS). These include two simple handling operations (Figures 2 & 3), a large and clearly visible control window and multiple safety and patient compliance features. In addition, Pro-Ject(TM) is very compact in size and light in weight, which is a real benefit in terms of transport, storage, and environmental footprint. Given its unique design, Pro-Ject(TM) can be easily adapted or tailored to specific therapy needs because the core technology provides design freedom to optimize the user interface.

 Pro-Ject(TM) also has unique visual and acoustic feedbacks for needle insertion and end-of-injection that allow for strong product differentiation. Pro-Ject(TM) design and development benefit from Aptar Pharma’s long experience of a Quality-by-Design approach, which translates into robust design, successful manufacturing scale-up, and flawless fast-track to market.

Q: What are the major design challenges that companies are likely to experience when designing and developing a novel auto-injector?

A: Designing and developing a novel auto-injector that meets all stakeholders’ criteria is a fascinating and complex journey. The “one-size-fits-all” approach is not realistic as there are many criteria to take into account beyond user needs and preferences, due to the range of drugs, drug formulations, therapies, and patient profiles that can be catered to.

Because the relationship between the drug, the prefilled syringe, and the auto-injector is highly complex, the design and development of the optimal solution present a number of technical and scientific challenges. This requires strong project management, which must allow experts to communicate and work together effectively.

Having recognized this, the objective of device designers is to create platform technologies that can leverage the robustness of proven technical building blocks. Designers want to improve effectiveness and safety while seeking manufacturing synergies to avoid high upfront investments during development and scale-up. Minimizing R&D expenses and capital expenditure are welcome in any project but become essential for generics and emerging markets in which cost effectiveness is a major priority.

Q: What are the market trends that are particularly relevant to self-injection?

A: New drugs and reformulations of existing drugs (in the case of life cycle management of existing drug products or biosimilars/generics) often provide a set of initial challenges. The injected drug volume and the drug viscosity, which may be interrelated, both influence the selection of the prefilled syringe format and specification (materials for the barrel, stopper and needle shield components, injection volume, needle size and profile, silicon lubrication, etc) and therefore the design of the auto-injector.

Optimization of current device designs and the search for patent-protected product differentiation are strong market drivers, together with specific needs related to therapies and patient profiles. Recently, we have seen some degree of technical convergence between prefilled syringes, safety-engineered syringes, pen injectors, auto-injectors, and needle-free injectors. There is no clear demarcation line between a traditional prefilled syringe and an “automatic” device anymore, and this allows a wide range of new designs to be developed. This explains the wide variety of the devices on offer as well as the number of patents referring to injectable devices or means, which is in excess of 3,000.

Given the emergence and penetration of smart devices in the medical sector, it is natural to see novel electronic injection devices flourishing and getting close to being used on the drug market. They offer almost unlimited possibilities in terms of user feedback, monitoring, and training, with devices talking to patients and/or data being transmitted to patients and physicians. They can incorporate programmable dosing of large injectable doses (between 1 and 2 ml, or even more in the case of micro infusors and patch injectors) and high-viscosity drugs to help the patient control the rate of injection. Given the complexity of these “edevices” and the fact they incorporate electronic components and batteries, they are also faced with specific regulatory and environmental challenges compared with any conventional mechanical device.